Relationship of dietary fat to glucose metabolism

The relationship between dietary fat and glucose metabolism has been recognized for at least 60 years. In experimental animals, high fat diets result in impaired glucose tolerance. This impairment is associated with decreased basal and insulin-stimulated glucose metabolism. Impaired insulin binding and/or glucose transporters has been related to changes in the fatty acid composition of the membrane induced by dietary fat modification. In humans, high-fat diets, independent of fatty acid profile, have been reported to result in decreased insulin sensitivity. Saturated fat, relative to monounsaturated and polyunsaturated fat, appears to be more deleterious with respect to fat-induced insulin insensitivity. Some of the adverse effects induced by fat feeding can be ameliorated with omega-3 fatty acid. Epidemiological data in humans suggest that subjects with higher intakes of fat are more prone to develop disturbances in glucose metabolism, type 2 diabetes or impaired glucose tolerance, than subjects with lower intakes of fat. Inconsistencies in the data may be attributable to clustering of high intakes of dietary fat (especially animal fat) with obesity and inactivity. Metabolic studies suggest that higher-fat diets containing a higher proportion of unsaturated fat result in better measures of glucose metabolism than high-carbohydrate diet. Clearly, the area of dietary fat and glucose metabolism has yet to be fully elucidated.     

Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU study

Aims/hypothesis. The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders. Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans. Methods. The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo. Results. Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10 %, p = 0.03) but did not change on the monounsaturated fatty acid diet ( + 2 %, NS) (p = 0.05 for difference between diets). Insulin secretion was not affected. The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion. The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median (37E %). Here, insulin sensitivity was 12.5 % lower and 8.8 % higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol (LDL) increased on the saturated fatty acid diet ( + 4.1 %, p < 0.01) but decreased on the monounsaturated fatty acid diet (MUFA) (–5.2, p < 0.001), whereas lipoprotein (a) [Lp(a)] increased on a monounsaturated fatty acid diet by 12 % (p < 0.001). Conclusions/interpretation. A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion. A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake ( > 37E %). [Diabetologia (2001) 44: 312–319] Received: 21 August 2000 and in revised form: 8 November 2000     

Relationship of dietary fat and serum cholesterol ester and phospholipid fatty acids to markers of insulin resistance in men and women with a range of glucose tolerance

High-fat diets are associated with insulin resistance, however, this effect may vary depending on the type of fat consumed. The purpose of this study was to determine the relationship between intakes of specific dietary fatty acids (assessed by 3-day diet records and fatty acid composition of serum cholesterol esters [CEs] and phospholipids [PLs]) and glucose and insulin concentrations during an oral glucose tolerance test (OGTT). Nineteen men and 19 women completed the study. Nine subjects had type 2 diabetes or impaired glucose tolerance. Fasting insulin correlated with reported intakes of total fat (r = .50, P < .01), monounsaturated fat (r = .44, P < .01), and saturated fat (r = .49, P < .01), but not with trans fatty acid intake (r = .11, not significant [NS]). Fasting glucose also correlated with total (r = .39, P < .05) and monounsaturated fat intakes (r = .37, P < .05). In multivariate analysis, both total and saturated fat intake were strong single predictors of fasting insulin (R2 approximately .25), and a model combining dietary and anthropometric measures accounted for 47% of the variance in fasting insulin. Significant relationships were observed between fasting insulin and the serum CE enrichments of myristic (C14:0), palmitoleic (C16:1), and dihomo-gamma-linolenic (C20:3n-6) acids. In multivariate analysis, a model containing CE 14:0 and percent body fat explained 45% of the variance in fasting insulin, and C14:0 and age explained 30% of the variance in fasting glucose. PL C20:3n-6 explained 30% of the variance in fasting insulin, and a model including PL C18:1n-11 cis, C20:3n-6, age and body fat had an R2 of .58. In conclusion, self-reported intake of saturated and monounsaturated fats, but not trans fatty acids, are associated with markers of insulin resistance. Furthermore, enhancement of dihomo-gamma-linolenic and myristic acids in serum CE and PL, presumably markers for dietary intake, predicted insulin resistance.     

The influence of dietary fat on insulin resistance

Dietary fat has been implicated in the development of insulin resistance in both animals and humans. Most, although not all, studies suggest that higher levels of total fat in the diet result in greater whole-body insulin resistance. Although, in practice, obesity may complicate the relationship between fat intake and insulin resistance, clinical trials demonstrate that high levels of dietary fat can impair insulin sensitivity independent of body weight changes. In addition, it appears that different types of fat have different effects on insulin action. Saturated and certain monounsaturated fats have been implicated in causing insulin resistance, whereas polyunsaturated and omega-3 fatty acids largely do not appear to have adverse effects on insulin action. Given the importance of insulin resistance in the development of diabetes and heart disease, establishing appropriate levels of fat in the diet is an important clinical goal.     

A Mediterranean and a high-carbohydrate diet improve glucose metabolism in healthy young persons

Aims/hypothesis: Insulin resistance usually precedes the diagnosis of Type II (non-insulin-dependent) diabetes mellitus. However, in most patients, the clinical expression of the disease could be prevented by dietary and lifestyle changes. We investigated the effects of a diet enriched in monounsaturated fatty acids (Mediterranean diet) and a low fat, high-carbohydrate diet on in vivo and in vitro glucose metabolism in 59 young subjects (30 men and 29 women). Methods: We carried out an intervention dietary study with a saturated fat phase and two randomized-crossover dietary periods: a high-carbohydrate diet and a Mediterranean diet for 28 days each. We analysed the plasma lipoproteins fractions, free fatty acids, insulin sensitivity and glucose uptake in isolated monocytes at the end of the three dietary periods. Results: In comparison to the saturated fat diet, the CHO and Mediterranean diets induced a decrease of LDL-cholesterol (p < 0.001) and HDL-cholesterol (p < 0.001). Steady-state plasma glucose decreased (p = 0.023) and basal and insulin-stimulated 2-deoxiglucose uptake in peripheral monocytes increased in both diets (CHO and Mediterranean), (p = 0.007) indicating an improvement in insulin sensitivity. Fasting free fatty acids plasma values were correlated positively with steady state plasma glucose (r = 0.45; p < 0.0001). In addition, there was an inverse correlation between the mean glucose of the steady state plasma glucose period and logarithmic values of basal (r = –0.34; p = 0.003) and insulin stimulated glucose uptake in monocytes (r = –0.32; p = 0.006). Conclusion/interpretation: Isocaloric substitution of carbohydrates and monounsaturated fatty acids for saturated fatty acids improved insulin sensitivity in vivo and in vitro, with an increase in glucose disposal. Both diets are an adequate alternatives for improving glucose metabolism in healthy young men and women. [Diabetologia (2001) 44: 2038–2043] Received: 19 February 2001 and in revised form: 9 July 2001     

Medium‐chain fatty acids ameliorate insulin resistance caused by high‐fat diets in rats

Background High dietary intake of saturated fat impairs insulin sensitivity and lipid metabolism. The influence of fatty acid chain length, however, is not yet fully understood, but evidence exists for different effects of saturated long‐chain (LC) versus saturated medium‐chain (MC) fatty acids (FA). Methods To investigate the effects of the FA chain length, male Wistar rats were fed high‐fat diets containing triacylglycerols composed of either MC‐ or LCFA for 4 weeks; rats fed maintenance diet served as a control. The animals underwent euglycemic hyperinsulinemic clamping or oral metabolic tolerance testing respectively; enzyme activities of mitochondrial (EC2.3.1.21 carnitine palmitoyl transferase) and peroxisomal (EC1.3.3.6 acyl‐CoA oxidase) FA oxidation were measured in liver and muscle. Results LCFA consumption resulted in higher fasted serum insulin and glucose concentrations compared to controls, while MCFA‐fed animals did not differ from controls. Insulin sensitivity was reduced by 30% in the LCFA group while the MCFA group did not differ from controls. Feeding MCFA resulted in the controls' lowered fasted and post‐prandial triacylglycerol concentration compared to LCFA, while triacylglycerol concentrations in muscle were higher in both high‐fat groups compared to controls. No diet‐induced changes were found in acyl‐CoA oxidase (ACO) activity (liver and muscle), while LCFA feeding significantly raised carnitine palmitoyltransferase activity. Conclusions The chain length of saturated fatty acids in isocaloric diets affects insulin sensitivity, lipid metabolism and mitochondrial fatty acid oxidation without influencing body weight. While dietary LCFA clearly impair insulin sensitivity and lipid metabolism, MCFA seem to protect from lipotoxicity and subsequent insulin resistance without caloric restriction. Copyright © 2009 John Wiley & Sons, Ltd.     

Substituting dietary saturated fat with polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity

Aims/hypothesis: British dietary recommendations are to decrease total fat intake to less than 30 % of daily energy intake and saturated fat to less than 10 %. In practice, it is difficult for people to make these changes. It may be easier to encourage people to switch from a diet rich in saturated fatty acids to one rich in polyunsaturated fatty acids. Methods: A total of 17 subjects – six people with Type II (non-insulin-dependent) diabetes mellitus, six non-obese and five obese people without diabetes – were randomised to spend two 5-week periods on a diet rich in saturated or in polyunsaturated fatty acids, in a crossover design. At the start of the study and after each dietary period, we assessed abdominal fat distribution using magnetic resonance imaging, insulin sensitivity using hyperinsulinaemic-euglycaemic clamps and fasting lipid parameters. Results: Dietary compliance, assessed by weekly 3-day dietary records and measurement of biochemical markers, was good. Energy and fat intake appeared to be reduced on the diet rich in polyunsaturated fatty acids although body weights did not change. Insulin sensitivity and plasma low density lipoprotein cholesterol concentrations improved with the diet rich in polyunsaturated fatty acids compared with the diet rich in saturated fatty acids. There was also a decrease in abdominal subcutaneous fat area. Conclusion/interpretation: If this result is confirmed in longer-term studies, this dietary manipulation would be more readily achieved by the general population than the current recommendations and could result in considerable improvement in insulin sensitivity, reducing the risk of developing Type II diabetes. [Diabetologia (2002) 45: 369–377] Received: 3 August 2001 and in revised form: 26 November 2001     

Differential effects of dietary saturated and trans-fatty acids on expression of genes associated with insulin sensitivity in rat adipose tissue

OBJECTIVE: Trans-fatty acids (TFAs) are formed during partial hydrogenation of vegetable oils and are shown to be more atherogenic than saturated fatty acids (SFAs). Our previous study showed that dietary TFAs decrease adipose tissue insulin sensitivity to a greater extent than SFAs in rats. We hypothesized that the effects of these fatty acids on insulin sensitivity could be mediated through an alteration in gene expression. In the current study we have investigated the effects of dietary TFAs or SFAs on expression of genes associated with insulin sensitivity in rat adipose tissue. DESIGN AND METHODS: Male weanling Wistar/NIN rats were divided into four groups and fed one of the following diets containing 10% fat (g/100 g diet) differing only in the fatty acid composition for 3 months: control diet (3.7% linoleic acid (LA)), SFA diet (5% SFA), TFA diet 1 (1.5% TFA + 1% LA) and TFA diet 2 (1.5% TFA + 2% LA). The mRNA expression of peroxisome proliferator-activated receptor gamma (PPARgamma), lipoprotein lipase (LPL), glucose transporter-4 (GLUT4), resistin and adiponectin was analyzed in epididymal fat using RT-PCR. The effects of TFA were studied at two levels of LA to understand the beneficial effects of LA over the effects of TFA. RESULTS: Both dietary SFA and TFA upregulated the mRNA levels of resistin. Dietary SFA downregulated adiponectin and GLUT4 and upregulated LPL, while TFA downregulated PPARgamma and LPL. The effects of dietary TFA on PPARgamma and resistin were not counteracted by increased LA (TFA diet 2). CONCLUSION: The effects of SFAs on the aforementioned genes except PPARgamma could be extrapolated towards decreased insulin sensitivity, while only the alteration in the mRNA levels of PPARgamma and resistin could be associated with insulin resistance in TFA-fed rats. These findings suggest that dietary SFAs and TFAs alter the expression of different genes associated with insulin sensitivity in adipose tissue.     

Diabetogenic impact of long-chain omega-3 fatty acids on pancreatic beta-cell function and the regulation of endogenous glucose production

In healthy individuals, peripheral insulin resistance evoked by dietary saturated lipid can be accompanied by increased insulin secretion such that glucose tolerance is maintained. Substitution of long-chain omega-3 fatty acids for a small percentage of dietary saturated fat prevents insulin resistance in response to high-saturated fat feeding. We substituted a small amount (7%) of dietary lipid with long-chain omega-3 fatty acids during 4 wk of high-saturated fat feeding to investigate the relationship between amelioration of insulin resistance and glucose-stimulated insulin secretion (GSIS). We demonstrate that, despite dietary delivery of saturated fat throughout, this manipulation prevents high-saturated fat feeding-induced insulin resistance with respect to peripheral glucose disposal and reverses insulin hypersecretion in response to glucose in vivo. Effects of long-chain omega-3 fatty acid enrichment to lower GSIS were also observed in perifused islets suggesting a direct effect on islet function. However, long-chain omega-3 fatty acid enrichment led to hepatic insulin resistance with respect to suppression of glucose output and impaired glucose tolerance in vivo. Our data demonstrate that the insulin response to glucose is suppressed to a greater extent than whole-body insulin sensitivity is enhanced by enrichment of a high-saturated fat diet with long-chain omega-3 fatty acids. Additionally, reduced GSIS despite glucose intolerance suggests that either long-chain omega-3 fatty acids directly impair the beta-cell response to saturated fat such that insulin secretion cannot be augmented to normalize glucose tolerance or beta-cell compensatory hypersecretion represents a response to insulin resistance at the level of peripheral glucose disposal but not endogenous glucose production.     

Trans fatty acids and insulin resistance

Since trans fatty acids (TFA) might interfere with cell membrane functions, there are reasons to believe that high TFA intakes could affect insulin sensitivity and consequently diabetes risk. It is possible that low amounts of TFA consumed during long time-periods might be clinically relevant. Data from controlled intervention studies investigating the effects of TFA on insulin sensitivity are reviewed. The results show no significant effect of TFA on insulin sensitivity in lean healthy subjects. However, there is some evidence that TFA could impair insulin sensitivity compared to unsaturated fat in insulin resistant or diabetic individuals. This is especially true for conjugated TFA, i.e. conjugated linoleic acid (CLA), which clearly impairs insulin sensitivity. In fact, the effect of CLA on insulin action is the most dramatic adverse effect described for a dietary fatty acid. The inconsistent effect of TFA as a group might partly be due to methodological limitations (e.g. few studies, short duration or small sample size) and differences between studies in design, type and amount of TFA used. Large controlled trials have been required to demonstrate adverse effects of saturated fat on insulin sensitivity, and similar efforts will probably be needed to clarify the effect of TFA on insulin sensitivity.     

Association of glutathione peroxidase activity with insulin resistance and dietary fat intake during normal pregnancy

Glutathione peroxidase (GPx) is one of the most important antioxidant enzymes in humans. We studied the relationship between erythrocyte GPx activity and fasting serum insulin, plasma glucose, and C-peptide, estimates of insulin resistance from the homeostasis model of assessment as well as dietary fat intake in 408 normotensive nondiabetic pregnant women from Camden, NJ. GPx activity and the metabolic parameters were determined at entry to care (16 wk of pregnancy) and during the third trimester. GPx activity and the levels of insulin resistance increased significantly between entry and the third trimester. Statistically significant associations, all positive, were observed between GPx activity and fasting insulin (beta = 0.009, P < 0.001), glucose (beta = 0.975, P < 0.05), C-peptide (beta = 1.537, P < 0.01), and insulin resistance from the homeostasis model of assessment (beta = 0.209, P < 0.01). Dietary intakes of fat and polyunsaturated fatty acids were positively correlated with GPx activity as well. African Americans had significantly higher GPx activity, dietary fat, and polyunsaturated fatty acid intake than Hispanics and Caucasians. In conclusion, we demonstrated that normal pregnancy is associated with increased GPx activity and insulin resistance. There are ethnic differences in antioxidant response and dietary fat intake. Our findings suggest a potential link among antioxidant defenses, insulin resistance, and dietary fat intake.     

The -514 C/T polymorphism in the hepatic lipase gene promoter is associated with insulin sensitivity in a healthy young population

Impaired insulin action has been associated with diabetes, dyslipidemia and atherosclerotic vascular disease. The expression of insulin resistance results from the interaction of environmental and genetic factors. Human hepatic lipase (HL) is a lipolytic enzyme that plays a role in the metabolism of several lipoproteins, while insulin up-regulates the activity of HL via insulin-responsive elements in the HL promoter. We have examined the influence of -514 C/T polymorphism in the hepatic lipase gene promoter on insulin sensitivity in 59 healthy young subjects (30 males and 29 females). The volunteers were subjected to three dietary periods, each lasting four weeks. During the first period all subjects consumed a saturated fat (SFA)-enriched diet with 38% as fat (20% SFA, 12% monounsaturated fatty acids (MUFA) and 6% polyunsaturated fatty acids (PUFA)). In the second and third dietary periods, a randomized crossover design was used, consisting of a low fat, high carbohydrate diet (CHO diet) (< 10% SFA, 12% MUFA and 6% PUFA) and a high-MUFA, or Mediterranean diet, with < 10% SFA, 22% MUFA and 6% PUFA. We determined the in vivo insulin resistance using the insulin suppression test with somatostatin. Steady-state plasma glucose (SSPG) concentrations (a measure of insulin sensitivity) were significantly higher in men carriers of the -514T allele after the consumption of the SFA diet than after the CHO diet and the Mediterranean diet. This effect was not observed in women. Moreover, there were no significant differences in insulin sensitivity after the three diets in men and women with the CC genotype. In summary, our results show an improvement in insulin sensitivity in men with the -514T allele of the HL promoter polymorphism, when MUFA and carbohydrates are consumed instead of SFA fat.     

Diet, insulin resistance, and obesity: zoning in on data for Atkins dieters living in South Beach

Insulin resistance is a central pathogenic factor for the metabolic syndrome and is associated with both generalized obesity and the accumulation of fat in the omental and intramyocellular compartments. In the context of the current obesity epidemic, it is imperative to consider diets in terms of their ability to both promote weight loss and ameliorate insulin resistance. Weight loss under any dietary formulation depends on hypocaloric intake, and only moderate weight loss (5-10%) is sufficient to augment insulin sensitivity. However, increments in insulin sensitivity may be more directly related to loss of intramyocellular or omental fat rather than loss of total body weight per se. The widespread acceptance of popular low-carbohydrate high-fat diets (e.g. Atkins Diet, Zone Diet, South Beach diet) further underscores the need to evaluate dietary interventions regarding their safety and metabolic effects. These high-fat diets have been shown to be safe in the short term; however, their long-term safety has not been established. With respect to insulin sensitivity, diets enriched in saturated fats can induce insulin resistance, whereas fat substitution with monounsaturated fats can enhance insulin sensitivity. On the other hand, high-fiber, high-carbohydrate diets comprised of foods with low caloric density can similarly be used for effective weight reduction and to ameliorate insulin resistance. Although some data suggest that low-glycemic index diets are most advantageous in this regard, these effects may have more to do with increments in dietary fiber than differences in available carbohydrates. Popular low-carbohydrate, high-fat diets are being fervently embraced as an alternative to challenging modifications in lifestyle and intentional calorie reduction. Current data do not support such unbridled enthusiasm for these diets, particularly in relationship to high-fiber, high-carbohydrate diets emphasizing intake of fresh vegetables and fruits. Long-term studies to determine the efficacy and safety of both popular and experimental diets are warranted.     

Dietary trans fatty acid

Trans fatty acids are unsaturated fatty acids that contain at least one double bond in the trans configuration. In the diet they occur at relatively low levels in meat and dairy products as a by-product of fermentation in ruminant animals or in hydrogenated fats as a consequence of the hydrogenation process. In general, dietary hydrogenated fat/trans fatty acids have been reported to increase LDL cholesterol levels relative to oil in the natural state or cis fatty acids. In contrast, dietary hydrogenated fat/trans fatty acids have been reported have to have little effect or decrease HDL cholesterol levels, the later observation restricted to relatively high intakes of trans fatty acids. These two effects result in higher, therefore less favorable, total or LDL cholesterol/HDL cholesterol ratios. Significant increases in Lp(a) levels have been reported after consumption of diets relatively high in trans fatty acids compared with either unsaturated or saturated fatty acids. However, the magnitude of the change is for the most part small and the physiological significance of this observation has yet to be resolved. Data related to the mechanism by which hydrogenated fat/trans fatty acids alter serum lipid levels and other risk factors for cardiovascular disease are in the nascent stages. At this time it would appear prudent that public health recommendations should be aimed at encouraging the moderate consumption of products low in saturated fat or minimally hydrogenated. Trans fatty acids intake should not be stressed at the expense of saturated fat but should augment it.     

Postprandial lipemia, diet, and cardiovascular risk

Recently published studies have provided additional evidence of the pathophysiology and clinical relevance of postprandial dyslipidemia. Notably, the relationship with cardiovascular risk has been considerably strengthened by two large prospective studies showing an independent role for nonfasting plasma triglycerides. Knowledge of the genetic influence has been expanded by the identification of new gene variants associated with postprandial lipemia. More data have confirmed the strict relation between postprandial lipoprotein alterations and insulin resistance, whereas studies on the association with endothelial dysfunction have not been conclusive. Recent medium-term intervention studies have mainly evaluated the different dietary fatty acids and compared diets rich in monounsaturated fatty acids with diets rich in carbohydrates. Results indicate that the diet generally recommended for cardiovascular prevention (ie, low in saturated fat, rich in omega-3 fatty acids, moderately rich in carbohydrates, and rich in fiber) may also correct postprandial lipid abnormalities.     

A high-trans fatty acid diet and insulin sensitivity in young healthy women.

Epidemiological and experimental studies suggest that a diet rich in saturated fat affects insulin sensitivity. Monoenes and dienes that have an usaturated bond with the trans configuration (trans fatty acids) resemble saturated fatty acids with respect to structure, but no published data are available on the effect of trans fatty acids on insulin sensitivity. Therefore, the effects of diets high in trans fatty acids (TFA diet) and oleic acid (monounsaturated fat [MUFA] diet) on glucose and lipid metabolism were studied in 14 healthy women. Subjects consumed both experimental diets for 4 weeks according to a randomized crossover study design. Both experimental diet periods were preceded by consumption of a standardized baseline diet for 2 weeks. The diets provided 36.6% to 37.9% of energy (E%) as fat. In the TFA diet, there was 5.1 E% trans fatty acids, and in the MUFA diet, 5.2 E% oleic acid, substituted for saturated fatty acids in the baseline diet. A frequently sampled intravenous glucose tolerance test (FSIGT) was performed at the end of the experimental diet periods. Glucose effectiveness (S(G)) and the insulin sensitivity index (S(I)) did not differ after the two experimental diet periods. There was also no difference in the acute insulin response between the diets. The total cholesterol to high-density lipoprotein (HDL) cholesterol ratio and serum total triglyceride, HDL, and low-density lipoprotein (LDL) triglyceride and apolipoprotein B (apoB) concentrations were higher (P < .05) after the TFA diet. In conclusion, in young healthy women, the TFA diet resulted in a higher total/HDL cholesterol ratio and an elevation in triglyceride and apo B concentrations but had no effect on glucose and insulin metabolism compared with the MUFA diet.     

Review: The role of insulin resistance in nonalcoholic fatty liver disease

CONTEXT: Insulin resistance is an almost universal finding in nonalcoholic fatty liver disease (NAFLD). This review outlines the evidence linking insulin resistance and NAFLD, explores whether liver fat is a cause or consequence of insulin resistance, and reviews the current evidence for treatment of NAFLD. EVIDENCE ACQUISITION: Evidence from epidemiological, experimental, and clinical research studies investigating NAFLD and insulin resistance was reviewed. EVIDENCE SYNTHESIS: Insulin resistance in NAFLD is characterized by reductions in whole-body, hepatic, and adipose tissue insulin sensitivity. The mechanisms underlying the accumulation of fat in the liver may include excess dietary fat, increased delivery of free fatty acids to the liver, inadequate fatty acid oxidation, and increased de novo lipogenesis. Insulin resistance may enhance hepatic fat accumulation by increasing free fatty acid delivery and by the effect of hyperinsulinemia to stimulate anabolic processes. The impact of weight loss, metformin, and thiazolidinediones, all treatments aimed at improving insulin sensitivity, as well as other agents such as vitamin E, have been evaluated in patients with NAFLD and have shown some benefit. However, most intervention studies have been small and uncontrolled. CONCLUSION: Insulin resistance is a major feature of NAFLD that, in some patients, can progress to steatohepatitis. Treatments aimed at reducing insulin resistance have had some success, but larger placebo-controlled studies are needed to fully establish the efficacy of these interventions and possibly others in reducing the deleterious effects of fat accumulation in the liver.     

Nutrition and physical activity in Asian Indians with non-alcoholic fatty liver: A case control study

AimWe tested the hypothesis that Asian Indians with non-alcoholic fatty liver disease (NAFLD) would have imbalanced diets and lower intensity of physical activity than those without NAFLD.MethodsWe studied dietary intake, intensity of physical activity and anthropometric and metabolic profiles in subjects with NAFLD and in healthy controls. Complete clinical, biochemical, dietary and physical activity profiles were studied for 169 cases and 173 controls in a prospective manner. Bivariate and multivariate analyses were carried out to identify the predictors of NAFLD [odds ratio (OR) and 95% confidence intervals (95%CI)].ResultsThe mean dietary intakes of total energy, carbohydrate, protein, total fat, saturated fat and total cholesterol were significantly higher, while intake of monounsaturated fatty acids and polyunsaturated fatty acids was significantly lower in cases as compared to controls (p < 0.01 for all). Further, mean physical activity in a day (expressed as MET.Minutes) and total energy expenditure were significantly lower in cases than in controls (33.3 ± 3.6 vs.36.2 ± 0.5, p = 0.001 and 2707.6 ± 505.6 vs. 2904.3 ± 690.3, p = 0.02, respectively). On multivariate analysis, percentage dietary total fat intake (OR: 13.4; 95% CI: 4.6–39.3, p = 0.001), homeostatis model assessment for insulin resistance (OR: 6.9; 95% CI: 3.2–14.8, p = 0.001) abdominal obesity (OR: 2.7; 95% CI: 1.5–5.0, p = 0.001) and high serum triglycerides (OR: 2.1; 95%CI: 1.2–3.8, p = 0.007) were associated with an increased risk for development of NAFLD.ConclusionDecrease in intake of total dietary fats and improvement of insulin resistance, abdominal obesity and blood triglycerides should be important measures for management of NAFLD in Asian Indians in north India.     

Dietary fatty acids modify insulin secretion of rat pancreatic islet cells in vitro

The type of dietary fat affects the action of insulin by changes induced in the fatty acid composition of cell membranes. Little is known, however, about the effects of dietary fatty acids on insulin secretion or the possible relation between the fatty acid composition of the membrane phospholipids and insulin secretion. We therefore studied the effects of dietary fatty acids on insulin secretion stimulated by glucose, forskolin and arginine, and on the insulin content of isolated pancreatic islets, as well as on the fatty acid composition of muscle phospholipids, which were used as markers of the diet-induced modifications in the cell membranes. Five groups of rats were fed for one month with diets varying only in their fat composition: olive oil, sunflower oil, soybean oil, fish oil and palmitic acid (16:0) + soybean oil (SAT). The SAT group had higher insulin secretion, independently of the secretagogue used. No significant differences were found in insulin content between the groups. The dietary fatty acids modified the fatty acid composition of the muscle phospholipids, both in endogenously synthesized fatty acids and in those which were unable to be synthesized by the organism. No statistically significant relation was found between insulin secretion and the content of certain fatty acids in the muscle phospholipids.